Aim: To determine whether beta-blockers (BBs) improve the overall survival (OS) of patients with metastatic non-small cell lung cancer (NSCLC). Materials and Methods: The medical charts of 107 patients with metastatic NSCLC were retrospectively assessed. Thirty-five patients (BB group) using BBs during chemotherapy (CT) were compared with 72 controls [control=(C) group] who did not use BBs following the diagnosis of NSCLC. The histological tumor subtype, performance status (ECOG), age, gender, smoking status, comorbidities, other medications and chemotherapeutics that were received in any line of treatment were recorded. We compared the overall survival (OS) of the patients in the BB and C groups. Results: The mean age of the patients was 61 years (range 42-81 years) and all patients were administered CT. The BB group was more likely to have HT and IHD and was more likely to use RAS blockers (p<0.01 for all) compared with the C group, as expected. The mean follow-up time was 17.8 months (range 1-102 months) for the entire group. The most commonly prescribed BB agent was metoprolol (80% of cases). At the time of the analysis, 74 (69%) of all patients had died. In the univariate analysis the median overall survival (OS) was 19.25 (${\pm}2.87$) months (95%CI: 13.62-24.88) in the BB group and 13.20 (${\pm}2.37$) months (95%CI: 8.55-17.85) in the C group (p=0.017). However, the benefit of BBs on survival disappeared in the multivariate analysis. Conclusions: The use of BBs during CT may be associated with an improved OS for patients with metastatic NSCLC.
Vasoactive intestinal polypeptide(VIP) and ${\beta}-adrenergic$ agonists have immunomodultory effects on the peripheral blood T-lymphocytes of rat through their own receptors. Both of them utilize the same signal transduction pathway. That is, the stimulatory guanine nucleotide binding protein(G protein) mediates the receptor-adenylyl cyclase coupling, producing intracellular increase of cyclic adenosine monophosphate(cAMP). In the previous experiment, propranolol, a ${\beta}-adrenergic$ receptor blocker, inhibited the VIP-induced protein phosphorylation in lymphocytes. However, propranolol could not block the effect induced by forskolin. Therefore, this study was designed to elucidate the mechanism of the inhibitory action of propranolol on the effects of VIP. Using peripheral blood lymphocytes of rats, the effect of propranolol on the receptor binding characteristics of VIP was observed. And the effects of propranolol were compared to the effects of timolol on the cAMP increase induced by isoproterenol, VIP or forskolin. The results obtained are as follows. 1) Receptor binding study showed no significant differences in the affinity or density of VIP receptor between the control and propranolol-pretreated groups. 2) VIP-induced increase of cAMP was inhibited by propranolol, but not by timolol. 3) Both propranolol and timolol suppressed the isoproterenol-induced cAMP increase. 4) Propranolol also inhibited the histamine-induced cAMP increase. 5) Propranolol did not inhibit the increase of cAMP stimulated by forskolin. 6) Lidocaine did not block the VIP-induced cAMP increase. These results show that the inhibitory mechanism of propranolol is not related to ${\beta}-adrenergic$ receptor or its membrane stabilizing effect, and it is suggested that propranolol can block the effects of VIP by inhibiting the intermediate step between the VIP receptor and adenylyl cyclase.
Background: Postoperative atrial fibrillation (AF) is a common complication after coronary artery bypass graft (CABG) surgery. Although postoperative AF is regarded as benign, transient and self-limited, it has been associated with increased morbidity, thromboembolic events and an increased duration and cost of hospitalization. Material and Method: From January 1994 to December 2007, 190 patients that had isolated CABG surgery were divided into two groups. Group 1 (n=139) involved those who had postoperative atrial fibrillation, and group 2 (n=51) did not have any such events. We reviewed the medical records retrospectively including the incidence of postoperative AF, patient characteristics, surgery related factors and the outcome of the patients with postoperative AF. Result: The frequency of postoperative AF was 26.8%, the conversion rate to regular sinus rhythm before discharge was 82.4%; 82.4% of the AF developed within the first three postoperative days. Although the postoperative AF group was significantly older and had a prolonged postoperative Intensive care unit (ICU) stay, there was no difference in the aortic crossclamp time or duration of hospitalization. No spontaneous defibrillation at declamping, and longer duration of cardiopulmonary bypass were significantly related to the development of postoperative AF. However, postoperative treatment with a beta blocker was associated with a decreased incidence of postoperative AF. The multivariate analysis showed that age and ICU stay were significantly associated with the development of POAF. Spontaneous defibrillation and postoperative beta blocker treatment were significantly associated with a decreased frequency of POAF. Conclusion: AF after CABG surgery is a common complication associated with increased morbidity and a longer ICU stay. Therefore, various strategies aimed at reducing AF, and its complications, such as postoperative treatment with a beta blocker should be considered.
The effects of noradrenaline on the spontaneous contraction recorded from a strip of mucosa-free antral circular muscle were studied in the guinea-pig stomach, and the changes in slow waves and membrane resistance were analyzed in order to elucidate the mechanism for the excitatory response to noradrenaline. Electrical responses of circular muscle cells were recorded using glass microelectrodes filled with 3 M KCI. Electrotonic potentials were produced to estimate membrane resistance by the partition stimulating method. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The spontaneous contractions were potentiated dose-dependently by the application of noradrenaline. 2) Through the experiments using adrenoceptor-blockers, the strong excitatory effect via $[\alpha}-adrenoceptors$ and the weak inhibitory efffect via ${\beta}-adrenoceptors$ were noted. 3) Noradrenaline produced hyperpolarization of membrane potential, and increases in the amplitude and the maximum rate of rise of slow waves. 4) In the presence of apamin, Ca-dependent K channel blocker, the characteristic hyperpolarization was not developed. However, the excitatory effect of noradrenaline on spontaneous contraction remained. 5) Membrane resistance was reduced during the hyperpolarized state by the application of noradrenaline, and the change of membrane resistance and the hyperpolarized state were completely abolished by apamin. From the above results, following conclusions could be made: Excitatory responses to noradrenaline result from the dominant ${\alpha}-excitatory$, and the weak ${\beta}-inhibitory$ action of noradrenaline. Hyperpolarization of membrane potential by noradrenaline is due to the activation of Ca-dependent K channel.
Background: Lack of proper control of acute postoperative pain often leads to lingering or chronic pain. Several studies have emphasized the role of beta-blockers in reducing postoperative pain. Esmolol is a selective short-acting beta-blocker that produces few side effects. The purpose of this study was to examine the effect of intravenous intraoperative esmolol on postoperative pain reduction following orthopedic leg fracture surgery. Methods: In a clinical trial, 82 patients between 20-65 years of age with tibia fractures and American Society of Anesthesiologists (ASA) physical status I & II who underwent surgery were divided into two groups. Group A received esmolol and group B received normal saline. Postoperative pain was measured at three time points: entering the recovery unit, and at 3 h and 6 h following surgery, using the Visual Analogue Scale (VAS). A P value of < 0.05 was considered significant. Results: Mean VAS scores at all three time points were significantly different between the two test groups (P = 0.02, P = 0.0001, and P = 0.0001, respectively). The consumption of pethidine was lower in group A than in group B (P = 0.004) and the duration of its effect was significantly longer in time (P = 0.026). Conclusions: Intravenous intraoperative esmolol is effective in the reduction of postoperative pain following leg fracture surgery. It reduced opioid consumption following surgery and delayed patient requests for analgesics.
The voltage clamp studies were undertaken to elucidate the properties of the slow inward current, $i_{si}$, in the small preparations of the rabbit sinoatrial node. The slow inward current, $i_{si}$, which is known to be responsible for the late one-third of pacemaker potential and whole range of upstroke phase of action potential was analysed with the effects of isoprenaline, cobalt, ouabain and higenamine. The results obtained are as follows; 1) Voltage of SA node preparation was held at zero current level, usually-40mV and the slow inward current, $i_{si}$, was activated by depolarizing clamp pulses. Peak values of $i_{si}$, in steady state were at $-10{\pm}0mV$ in most preparations. 2) Isoprenaline, ${\beta}-agonist$ increased $i_{si}$ and no shift was noticed in voltage-dependency. 3) Cobalt ion in the concentration of 1 mM abolished is, in entire range of membrane potential and the difference of two current levels before and after $Co^{2+}$ treatment could be considered as pure $i_{si}$ magnitude. 4) In the therapeutic concentration of ouabain $(5{\times}10^{-8}M)$ slightly increased is, and reduced the time to reach the peak value. 5) Higenamine $(10^{-6}M)$ changed the configurations of action potential (i. e. rapid upstroke phase and notch in the spike) and increase spontaneous rate. It also increased is, and the effect of higenamine was blocked ${\beta}-blocker$, propranolol $(10^{-6}M)$.
The International Society for the Study of Vascular Anomalies classifies vascular anomalies into vascular tumors and vascular malformations. Vascular tumors are neoplasms of endothelial cells, among which infantile hemangiomas (IHs) are the most common, occurring in 5%-10% of infants. Glucose transporter-1 protein expression in IHs differs from that of other vascular tumors or vascular malformations. IHs are not present at birth but are usually diagnosed at 1 week to 1 month of age, rapidly proliferate between 1 and 3 months of age, mostly complete proliferation by 5 months of age, and then slowly involute to the adipose or fibrous tissue. Approximately 10% of IH cases require early treatment. The 2019 American Academy of Pediatrics clinical practice guideline for the management of IHs recommends that primary care clinicians frequently monitor infants with IHs, educate the parents about the clinical course, and refer infants with high-risk IH to IH specialists ideally at 1 month of age. High-risk IHs include those with life-threatening complications, functional impairment, ulceration, associated structural anomalies, or disfigurement. In Korea, IHs are usually treated by pediatric hematology-oncologists with the cooperation of pediatric cardiologists, radiologists, dermatologists, and plastic surgeons. Oral propranolol, a nonselective beta-adrenergic antagonist, is the first-line treatment for IHs at a dosage of 2-3 mg/kg/day divided into 2 daily doses maintained for at least 6 months and often continuing until 12 months of age. Topical timolol maleate solution, a topical nonselective beta-blocker, may be used for small superficial type IHs at a dosage of 1-2 drops of 0.5% gel-forming ophthalmic solution applied twice daily. Pulse-dye laser therapy or surgery is useful for the treatment of residual skin changes after IH involution.
Background: To improve sinus rhythm conversion, the Cox maze III procedure with narrow mazes (width: ${\leq}3.0cm$) was performed in combination with left atrial volume reduction. Methods: From October 2007 to April 2013, 87 patients with atrial fibrillation (paroxysmal in 3, persistent in 14, and permanent in 70) underwent the Cox maze procedure concomitant with another cardiac procedure. They were followed-up with serial electrocardiographic and echocardiographic studies. We used 24-hour Holter monitoring tests to evaluate postoperatively symptomatic patients. Results: At the mean follow-up time of 36.4 months, 81 patients (94.2%) had sinus rhythm and two were on anti-arrhythmic medication (one on a beta-blocker and the other on amiodarone). Five patients (5.8%) with postoperative recurrent and persistent atrial fibrillation never experienced sinus rhythm conversion; however, they did not require any medication for rate control. On postoperative echocardiography, the left atrial A waves were more frequently observed after concomitant mitral valve repair than after concomitant mitral valve replacement (82.4% vs. 40.4%, respectively; p<0.001). Conclusion: For the Cox maze procedure, narrow mazes and atrial volume reduction resulted in excellent sinus rhythm conversion without the preventive use of anti-arrhythmic drugs, and they did not affect the presence of the left atrial A waves on echocardiography.
Purpose: Health Insurance Review & Assessment Service (HIRA) launched an Acute Myocardial Infarction(AMI) assessment for the Payment For Performance(Quality Incentives) Pilot Project from July 2007. Assessment measures of AMI were composed of five process measures and one outcome measure, and each measure was incorporated into one composite quality score to Pay for Performance. Method: For calculation of composite quality score, we considered weighting for the measures using the Delphi method. The questionnaire was composed of three measure groups, 'Reperfusion rate'(Fibrolytic therapy received within 60 minutes of hospital arrival, Primary Percutaneous Coronary Intervention within 120 minutes of hospital arrival), 'Medication prescription rate'(Aspirin at arrival, Aspirin prescribed at discharge, Beta-blocker prescribed at discharge) and 'Survival Index'(30-day mortality rate). Result: A panel composed of 18 and completed a questionnaire by allocation of 10 scores to the three above mentioned measure groups. The Delphi was carried out until three rounds of surveys. In conclusion, each measure group was weighted differently and the 10 scores were allocated as 4.5 to 'Reperfusion rate', 2.5 to 'Medication prescription rate', and 3.0 to 'Survival Index'. Conclusion: The results of this study proposed the calculation method for weighting of Acute Myocardial Infarction quality indicators.
Six medicinal plants described in Dong-Ee-Bo-Gam as to be useful for hypertension treatment were evaluated their antihypertensive activity against Okamoto-SHR, an animal model of spontaneous hypertension. Ethanol extracts of plant samples were prepared and were p.o. administered once daily for 20 days. Average blood pressures of rats were measured during two weeks periods before drug administration. Then blood pressure of each rat was measured every three days during drug administration period. As a positive control, propranolol, ${\beta}-blocker$ was used and the blood pressures of test group rats were compared with those of negative and positive control group rats. Among 6 plant extracts, Acanthopanax sessiliflorum and Atractylodes japonica (alba) extracts appeared to exhibit antihypertensive activity.
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